AMBER/PBSA: An Open-Source Computer Program for Accurate and Scalable Solvation A

描述（由申请人提供）：该项目的目标是继续开发和维护AMBER/PBSA程序，用于复杂生物分子系统的溶剂介导的能量学和动力学分析。生物分子通常在盐水环境中发挥作用，这对其结构和功能有很大影响。水的介电常数约为80，而生物分子内部的介电常数低至2。这导致原子电荷和高介电水之间的有利相互作用。另一方面，高介电水屏蔽或减少原子电荷之间的相互作用。水也会产生疏水效应，即水分子将非极性溶质聚集在一起的趋势。这促进了生物分子的自组装或不同生物分子之间的非极性表面的缔合。这些溶剂化效应通常是用隐式溶剂化方法模拟的，用于生物分子的高性能能量学和动力学分析。广泛使用的AMBER/PBSA程序是用于生物分子的隐式溶剂化处理的开源计算机程序。在这个项目中，我们提出了改进的AMBER/PBSA计划，采用先进的数值算法，并扩展其功能上现成的串行和并行计算平台。我们建议实施新的算法，以实现准确性和效率之间的更好的平衡，开发新的后分析方法，更强大的生物分子动力学建模，并探索新的介电模型，更多的物理治疗隐式溶剂化。最后，我们将继续严格验证隐式溶剂，并扩展软件界面，以吸引更多的用户。 公共卫生相关性：溶剂化在所有基本的生物分子事件中起着重要的作用，因此是生物分子结构和功能建模的组成部分。本申请旨在继续开发一种通用的分子建模软件，用于精确和可扩展的溶剂化处理。开发的软件模块将用于研究生物分子的结构、动力学和功能之间的关系，这对于合理的药物设计至关重要。

DESCRIPTION (provided by applicant): The goal of this project is to continue the development and maintenance of the AMBER/PBSA program for the solvation-mediated energetics and dynamics analysis of complex biomolecular systems. Biomolecules normally function in a salt-water environment, which has a strong effect on their structure and function. Water has a dielectric constant of about 80, whereas the dielectric constant of biomolecular interior is as low as 2. This leads to favorable interactions between atomic charges and the high-dielectric water. On the other hand, the high-dielectric water screens or reduces interactions among atomic charges. Water also gives rise to the hydrophobic effect, the tendency of water molecules to drive nonpolar solutes together. This promotes the self-assembly of biomolecules or association of nonpolar surfaces between different biomolecules. These solvation effects are often modeled with the implicit solvation methods for high-performance energetics and dynamics analysis of biomolecules. The widely used AMBER/PBSA program is an open-source computer program for implicit solvation treatments of biomolecules. In this project, we propose to improve the AMBER/PBSA program by incorporating advanced numerical algorithms and expanding its functionalities on readily available serial and parallel computing platforms. We propose to implement novel algorithms to achieve a better balance between accuracy and efficiency, develop new post-analysis methods for more robust modeling of biomolecular dynamics, and explore new dielectric models for more physical treatments of implicit solvation. Finally, we will continue our rigorous validation of implicit solvents and extend software interface to attract more users. PUBLIC HEALTH RELEVANCE: Solvation plays an important role in all basic biomolecular events and therefore is integral to the modeling of biomolecular structure and function. This application intends to continue the development of a general molecular modeling software for accurate and scalable treatment of solvation. The developed software module will be used to study the relation between structure, dynamics, and function of biomolecules, which is crucial for rational drug design.